EP2856178A1 - Dissolution guided wetting of structured surfaces - Google Patents
Dissolution guided wetting of structured surfacesInfo
- Publication number
- EP2856178A1 EP2856178A1 EP20130796502 EP13796502A EP2856178A1 EP 2856178 A1 EP2856178 A1 EP 2856178A1 EP 20130796502 EP20130796502 EP 20130796502 EP 13796502 A EP13796502 A EP 13796502A EP 2856178 A1 EP2856178 A1 EP 2856178A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- glucose
- gas
- pdms
- solution
- wetting
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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- RCHUVCPBWWSUMC-UHFFFAOYSA-N trichloro(octyl)silane Chemical compound CCCCCCCC[Si](Cl)(Cl)Cl RCHUVCPBWWSUMC-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 239000012808 vapor phase Substances 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000010148 water-pollination Effects 0.000 description 1
- 238000003631 wet chemical etching Methods 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M23/00—Constructional details, e.g. recesses, hinges
- C12M23/02—Form or structure of the vessel
- C12M23/16—Microfluidic devices; Capillary tubes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
- B81C1/00—Manufacture or treatment of devices or systems in or on a substrate
- B81C1/00015—Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems
- B81C1/00206—Processes for functionalising a surface, e.g. provide the surface with specific mechanical, chemical or biological properties
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M23/00—Constructional details, e.g. recesses, hinges
- C12M23/02—Form or structure of the vessel
- C12M23/12—Well or multiwell plates
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
- C12M29/20—Degassing; Venting; Bubble traps
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0684—Venting, avoiding backpressure, avoid gas bubbles
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/12—Specific details about manufacturing devices
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/16—Surface properties and coatings
- B01L2300/161—Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
- B81B2201/00—Specific applications of microelectromechanical systems
- B81B2201/05—Microfluidics
- B81B2201/058—Microfluidics not provided for in B81B2201/051 - B81B2201/054
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
- G01N2035/00099—Characterised by type of test elements
- G01N2035/00158—Elements containing microarrays, i.e. "biochip"
Definitions
- the present invention concerns micro-fabricated devices and methods of wetting gas- entrapping features therein.
- a new microfluidic design called a phaseguide, based on a step-wise advancement of the liquid-air interface using the meniscus pinning effect, can effectively eliminate the probability of trapping air bubbles in complex microfluidic geometries such as corners and deep angular structures. 6
- this method is difficult to remove txapped air in microcavities microwells, or dead ends, since it relies on the creation of strips of material on the wail along the direction of advancing fluid.
- a first aspect of the invention is a microfabricated device (e.g., a microwell array, a microfluidic device) having at least one gas-entrapping feature on a structured surface formed therein that, entraps gas bubbles which prevent the wetting of said feature with a solvent or solution.
- the device includes a sacrificial residue in contact with said gas entrapping feature.
- the nature of the sacrificial residue may be either hydrophilic or hydrophobic, and may be either a solid or a combination of a solute and solvent suitable for the gas -entrapping feature to be wetted.
- the gas-entrapping feature comprises a microwell, corner, microcavity, dead end, post, trap, hole, passage, channel, or combination thereo
- the surface of the gas entrapping feature is oxidized (e.g., plasma oxidized),
- a further aspect of the invention is a method of wetting a microfabricated device while inhibiting the entrapment of gas bubbles therein, comprising; (a) providing a microfabricated device as described herein, (b) treating the microfabricated device by priming it with a sacrificial residue in contact with the gas-entrapping features, and then (c) treating said microfabricated device with a solvent or solution sufficient to dissolve and remove said sacrificial residue from said gas-entrapping feature while concurrently wetting said gas entrapping feature with said solvent or solution.
- FIG. 2 Priming the hydrophilic microweils with glucose. SEM and brightfield images showing a micro well (D - 200 ⁇ , H - 55 ⁇ filled with a glucose solution and then dried. The volumetric concentration of glucose was varied as shown in the figure. SEM images were obtained at a tilt angle of 30°.
- FIG. 3 Dissolution guided wetting in microweils.
- C Time-lapse fluorescence images showing the dissolution of glucose (mixed with 200 pg/mL TRiTC dextran) in a microweil array (D - 200 pm, H - 55 ⁇ ).
- FIG. 4 Dissolution guided wetting in corners and dead ends of microfiuidic channels,
- A Air bubble entrapment was present in comers (/ ' ) and dead ends (/?) of PDMS microfiuidic channels on day 7 after bonding.
- B Priming the corners (/ ' , H) with glucose, and dead ends (Hi, iv) with sorbitol. Transmitted light (? ' and Hi) and fluorescence (if and vi) images clearly show the corners and dead ends were occupied with sugar. The sugar was mixed with 200 TRITC dextran for fluorescence imaging.
- C Time-lapse transmitted light images showing the dissolution of glucose in comers (/ ' ) and sorbitol in dead ends (if). Arrows indicate the direction of water flow. Prior to test, the channels were stored at room temperature in air for one week. Scale bar - 50 ⁇ « ⁇ .
- Figure 5 Schematic showing that the drying of glucose solution in a micro well results in a conformal, elliptical, cone-shaped coating of solid glucose. The degree of coverage depends on the concentration of glucose.
- FIG. 7 Transmitted light images showing glucose guided wetting in microwells formed in polystyrene. Scale bar - 100 ⁇ ,
- Figure 9 Process of priming the corners and dead ends of microfluidic channels with a 30 vol.% glucose solutio or a 50 vol% sorbitol solution.
- FIG. 10 Shape of glucose residue in PDMS microwells is dependent on the interfacial property of PDMS/glucose solution.
- A Schematic showing the wetting of glucose solution in a PDMS mierowell upon drying. The contact angle ⁇ determines the shape of glucose.
- B A parabolic residue of glucose is formed on an oxidized, hydrophilic PDMS.
- C A flat, column shaped residue of glucose is formed on a native, hydrophobic PDMS.
- FIG. 11 Wetting of microraft array without (A) and with (B) deposition of glucose residue, (i) Schemes of cross-sectional view of a raft, (ii) Schemes of wetting on a raft, (iii) Transmitted light images showing wetting on a raft array.
- Each well has a dimension of 200 ⁇ x 200 ⁇ ⁇ 100 ⁇ (length ⁇ width ⁇ height).
- a 40 wt% glucose solution was applied on the raft array followed by aspiration to remove excess solution and drying in air.
- the device may otherwise be oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly, Similarly, the terms “upwardly,” “downwardly,” “vertical,” “horizontal” and the like are used herein for the purpose of explanation only, unless specifically indicated otherwise.
- first, second, etc. may be used herein to describe various elements, components, regions, layers and/or sections, these elements, components, regions, layers and/or sections should not be limited by these terras. Rather, these terms are only used to distinguish one element, component, region, layer and/or section, from another element, component, region, layer and/or section. Thus, a first element, component region, layer or section discussed herein could be termed a second element, component, region, layer or section without departing from the teachings of the present invention.
- the sequence of operations (or steps) is not limited to the order presented in the claims or figures unless specificall indicated otherwise.
- Devices of the present invention are, in general, microfabricated devices such as mlcrowell arrays and microfluidic devices formed from or in a selected substrate. Such devices are known and examples include, but are not limited to, those described in US Patents Nos. 7,927,830; 7,775,088; 7,742,662; 7,556,776; 7,169,577; 7,161,356; 6,670,133; and 6,632,655.
- the microfabricated devices have one or more fluid passages, chambers, channels, wells, conduits or the like that are configured to contain microvolumes of liquids, typically wherein one or more of the dimensions is less than 500 ⁇ , in some embodiments, the device further comprises a main channel in fluid communication with the gas-entrapping feature; wherein the surface of said main channel is substantially free of the sacrificial residue.
- the device comprises a microfluidic network, with the gas-entrapping feature comprising a first region of th microfluidic network
- Devices of the invention can be formed from any suitable substrate material including but are not limited to silica based substrates, such as glass, quartz, silicon or polysiiicon, as well as other substrate materials, such as gallium arsenide and the like.
- suitable materials include but are not limited to polymeric materials, e.g., plasties, such as polymethylmethacrylate (PMMA), polycarbonate, polytetrafiuoroethylene (e.g., TEFLONTM), po!yvmyjchloride (PVC), polydimethyisiloxane (PDMS), polysulfone, polystyrene, polycarbonate, polyimide, cyclic-olefm copolymer, pol methyipentene, polypropylene, polyethylene, polyvinylidme fluoride, acrylonitrile-butadiene-styrene copolymer (ABS), and the like, as well as polymerized photoresists . , e.g., SU-8, 1002F and the like (see, e.g., US Patent No. 6,103,446).
- PMMA polymethylmethacrylate
- PVC polytetrafiuoroethylene
- PVC po!
- Substrate materials are often selected based upon their compatibility with known techniques, such as mic-rofabrication. Suitable substrate materials are also generally selected for their compatibility with the full range of conditions to which the microfabricated devices may be exposed, including extremes of pH, temperature, salt concentration, and application of electric fields. Accordingly, the substrate material may include materials normally associated with the semiconductor industry. In the case of semiconductive materials, it will often be desirable to provide an insulating coating or layer, e.g., silicon oxide, over the substrate material, and particularly in those applications where electric fields are to be applied to the device or its contents.
- an insulating coating or layer e.g., silicon oxide
- the substrates used to make the mircofabrieated device are silica-based, more preferably glass or quartz, due to their inertness to the conditions described above, as well as the ease with which they are microfabricated.
- polymeric substrate materials are preferred for their ease of manufacture, low cost and disposability, as well as their general inertness to most extreme reaction conditions.
- These polymeric materials may include treated surfaces, e.g., derivatized or coated surfaces, to enhance their utility in the microfluidic system, e.g., provided enhanced fluid direction, e.g., as described in U.S. Pat. No. 5,885,470, and which is incorporated herein by reference in its entirety for all purposes.
- the microfabricated device is made using a combination of materials, such as silica-based and polymeric materials.
- the material of the microfabricated device may be opaque, translucent or transparent.
- the device can be formed of a single layer substrate of a single material or a laminated or multi-layer configuration of the same or different material substrates.
- the device may be a single layer monolithic substrate or (more typically) a multiple layer device (e.g., having two or three layers or more) and having a thickness that is between about 0.2 mm to about 15mm.
- the thickness of the device is not critical, as the thickness of top and bottom parts of the device are not critical, so long as the proper inner chamber dimensions are provided for the intended use.
- the device can comprise a bioactive agent that is formed in a matrix of the substrate and/or applied or coated on a primary surface thereof to define one or more analytical sites on the device for analysis and/or to define a barrier zone.
- Microfabricated devices of the invention can be made by any suitable technique including but not limited to microfabrication techniques such as photolithography, wet chemical etching, laser ablation, reactive ion etching (RIE), air abrasion techniques, injection molding, L!GA methods, metal electroforming, embossing, and other techniques. Suitable techniques may also be those employed in the semiconductor industry. Other suitable techniques include but are not limited to molding techniques, such as injection molding, embossing or stamping, or by polymerizing the polymeric precursor material within the mold (See U.S. Pat No. 5,512, 131).
- Microfabricated devices may have either hydrophobic or hydrophilic surfaces. Further, hydrophobic surfaces can be made hydrophilic by treatment with air or oxygen plasma, chemical surface modification, or physical surface deposition.
- PDMS is a hydrophobic material and its hydrophobic surface can be made hydrophilic by oxygen plasma treatment (See Bodas D.and han-Maiek, C. Microelectronic Engineering, 2006,. 83, 1277-1279), or by chemical grafting of a thin hydrophilic poly(acrylie acid) on a hydrophobic PDMS surface (See U.S. Pat. No. 6596346 and Analytical Chemistry, 2002, 74, 41 17-4123), or by physical deposition of a glass layer (See A bate, A. et al.. Lab Chip, 2008, 8, 516-518).
- Microfabricated devices frequently contain gas-entrapping features such as microwells, microcavities, dead ends, corners, posts, holes, channels, traps, and passages.
- gas refers to any substance in the gaseous phase and may include nitrogen, oxygen, carbon dioxide, or mixtures such as air.
- the microfabricated devices are primed with a sacrificial residue that is suitable for dissolution guided wetting of the gas-entrapping features and therefore remove or prevent the formation of gas bubbles in the device.
- the sacrificial residue may be comprised of any suitable material, including but not limited to salts, carbohydrates (e.g., monosaccharide, ⁇ saccharide, oligosaccharide, or polysaccharide), and other hydrophilic polymers.
- the sacrificial residue is comprised of a non-metabolizable sugar (e.g., sorbitol, xylite I or mamutol, etc.).
- a salt that is readily dissolved i an aqueous solution may be used.
- Non-limiting examples of such a salt are sodium chloride, potassium chloride, sodium sulfate, sodium bisulfate, sodium phosphate, monosodium phosphate, disodlum phosphate, potassium phosphate, monopotasstum phosphate, dipotassium phosphate, calcium chloride, magnesium chloride, or a combination thereof.
- the sacrificial residue is, in some embodiments, amorphous.
- a suitable material thai is hydrophobic should be chosen for the sacrificial residue.
- suitable hydrophobic materials are hydrophobic polymers, low molecular weight organic solids, non-volatile liquids.
- hydrophobic polymers include, but are not limited to, polyethylene, polypropylene, polyvinyl chloride, polystyrene, nylons, polyesters, acrylics, polyurethane, and polycarbonates, polylactic acid, poiy(lactic-co- glycolic acid). poly(methyl methacrylate).
- low molecular weight organic solids include, but are not limited to, paraffin wax, naphthalene, anthracene, aspirin (acetylsalicylic acid), 2-naphthoI, fat.
- non-volatile liquids include, but are not limited to, synthetic oils (for example mineral oil), vegetable oils (for example olive oil), lipids, silicone oil, liquid epoxy resin.
- the sacrificial residue is a suitable solute thai is dissolved inan aqueous or non-aqueous solvent, contacting the selected solution comprising the solvent and solute with the gas- entrapping feature to be primed, and allowing the solution to dry thereon thereby depositing the solute in contact with the gas-entrapping feature.
- a material for the sacriflcial residue may be dispersed, rather than dissolved, in a suitable aqueous or nonaqueous solvent.
- the sacrificial layer is comprised of a solid material that may be brought into contact with a gas-entrapping feature as a fine particulate dust" and/or by melting the solid at a suitable temperature.
- the sacrificial residue used to achieve dissolution guided wetting of the structured surface does not chemically modify the surface. While plasma oxidation of the PDMS surface can be used in certain embodiments, this step to modify the surface is not required as the application of vacuum or solvents with the appropriate characteristics could be used to provide Wenze!-state wetting of the structured surface in the deposition of the sacrificial residue in. contact with gas-entrapping features.
- the primed microfabricated devices may be packaged in a water-proof container, and/or packaged in a container with a deslceant, for subsequent use.
- the primed microfabricated devices are typically rinsed, depending on its intended purpose, with an aqueous or non-aqueous rinse solution for a time, in an amount and at a temperature sufficient to dissolve and remove the sacrificial residue from said gas entrapping feature, and preferably while concurrently wetting said gas entrapping feature with said rinse solution.
- the device may then be rinsed with a second aqueous or nonaqueous solution (e.g., a growth media, an assay or reagent media, a reaction media, etc.) to remove the previous rinse solution therefrom and ready the device for its intended purpose.
- a second aqueous or nonaqueous solution e.g., a growth media, an assay or reagent media, a reaction media, etc.
- a method is described to prevent or eliminate gas bubbles on structured surfaces of microfabricated devices possessing microcavities, corners, dead ends and other gas- entrapping features.
- a microfabricated device was made using PDMS.
- the process for priming the microfabricated device for dissolution guided wetting of gas- entrapping features was composed of two steps: the surface was first made hydrophilic by plasma treatment, then primed with an aqueous monosaccharide solution, and placed in dry storage. Prior to use of the microfabricated device, the end user simply adds water to dissolve a monosaccharide followed by rinsing to remove any trace of the monosaccharide in the microfabricated device or in solution.
- the dissolution of the monosaccharide guides a complete wetting of the gas-entrapping features, leaving the structured surfaces tree of gas bubbles.
- Microwells and microfluidic channels made from PDMS were used as the model to demonstrate this dissolution-guided wetting of the gas-entrapping features.
- D-glucose, D-sorbitoi, phosphate buffered saline (PBS) tablets, tetramethylrhodaxnine isothiocyanate-dextran (TRITC-dextran, average molecular weight 500,000), and octyltrichiorosilane were purchased from Sigma Aldrich (St. Louis, MO).
- SU-8 photoresist was purchased from MicroChem Corp, (Newton, MA).
- PDMS was prepared from the Sylgard 184 silicone elastomer kit (Dow Corning, Midland, MI),
- PDMS a polymer known to have a rapid and complete hydrophobic recovery 5 was selected as the material to create the structured surfaces of the microwells and microfluidic channels.
- Microwell arrays and microfluidic channels were fabricated by micromolding PDMS on an SU-8 master by conventional soft lithography.”
- the S.U-8 master was fabricated by standard photolithography on a glass slide spin-coated with an SU-8 layer of 55 ⁇ thickness, 22
- the master mold was Created with 50 ⁇ octyltrichlorosilane in a vapor- phase silanization process in a polycarbonate desiccator (Fisher Scientific): the desiccator was degassed by art oil-free pump for 2 min and then closed for 16 h, PDMS prepolymer ( 10: 1 mixture of ase:curing ⁇ agent in the Sylgard 184 kit) was spread on the master mold and degassed under vacuum to remove air bubbles from the polymer.
- the master was baked at 100 °C on a hotplate for 30 min to cure the PDMS.
- the PDMS forming the micro well arrays or microchannels was then obtained by peeling it from the master.
- the depth of the microwells was 55 ⁇ ⁇ , and the diameter was in the range from 10 ⁇ to 3 mm.
- mieroiluidie channels holes of 2-mm diameter were first punched at the ends of the patterns on PDMS to serve as solution reservoirs.
- the PDMS and a glass slide were treated in an air-plasma cleaner (Harrick Plasma, Ithaca, NY) for 2 min before they were sealed to form an enclosed mieroiluidie channel
- the degree of wetting of the ga -entrapping features was determined by measuring the water contact angle.
- the water contact angle was measured with a pocket Goniometer PG-3 (Fibro system AB, Sweden) using a 5 ⁇ drop of deionized water. The contact angle was measured at 5 s after the drop was applied. An average of 10 measurements was calculated per surface.
- Microwells were primed with glucose as the sacrificial residue.
- Glucose solutions in water of different volumetric concentrations (0%, 22%, 30%, and 37%) were prepared.
- the volumetric concentration of glucose was calculated from its weight concentration by assuming the volume of solution is the sum of the volumes of the solute and solvent, PDMS microwell arrays were first treated in an air-plasma for 2 min to generate hydrophilic surfaces by oxidation.
- An open chamber was created surrounding the array using a self-sealing, square PDMS ring (25 x 25 x 6 mm) attached to the substrate.
- An aqueous solution of glucose (1-2 ml.-) was added to the chamber to wet the array surface.
- the sugar solution trapped in corners and dead ends within the device was allowed to gradually dry over 1 -2 days by evaporation.
- a 30 voi% glucose solution was used to till the corners in a microiluidic channel.
- a 50 vol% sorbitol solution was used, to fill the dead ends in a microiluidic channel where sorbitol was found, to be more effective due to the higher solubility of sorbitol in water.
- the wetting behavior (complete wetting, partial wetting, or non-wetting) of PDMS microwell arrays and microfiuidic channels, either primed with glucose or not, was determined by adding water and observing the presence of trapped air bubbles under a microscope. Air bubbles in the microwells and microiluidic channels were readily discerned by brightfield microscopy by virtue of a thick dark boundary being formed between air and PDMS due to differences in the refractive indices of water (1.33), PDMS (1.43) 23 and air (1 ,00), ' Similarly, deposition of glucose in the microwells and microfiuidic channels could be ascertained due to refractive index mismatches of air (1.00), PDMS (1.43) and glucose (1.53).
- the glucose solution was mixed with 200 ⁇ -.
- TRITC-dextran and used to prime microwells and microfiuidic channels.
- the microwells and microfiuidic channels were imaged using the Nikon Eclipse TJE300 microscope equipped with a CY3 filter set (G-2E; Nikon Instruments; excitation filter 528-553 nm dichroic 565 nra long pass, emission 590 -650 nm).
- Time lapse images were collected with a cooled CCD camera (Photometrix Cool Snap; Roper Scientific, Arlington, AZ) using NiS-Elements software. Air bubbles are often trapped in raicrofabricated devices.
- PDMS has the most rapid hydrophobic recovery.
- the water-droplet contact angle on PDMS films immediately after plasma treatment was 10° ⁇ 5°, but recovered to 42° ⁇ 8° (n - 3) after 3 days.
- the stability or duration of air trapping inside the wells was also dependent on the hydrophobieity of the PDMS.
- the priming of hydrophilic microwells with glucose can prevent the trapping of air bubbles in microcavities through dissolution guided wetting eliminates a significant annoyance in the use of microwell arrays for a standard biology lab.
- end users prefer to have devices in a ready-to-use state without the need for pre-processing immediately prior to the biological application.
- a fully wettable surface without the need for plasma oxidation, high vacuum exposure, or pre- treatment with a toxic, low-viscosity liquid such as ethanol would facilitate their use and acceptance.
- PDMS microwells were first oxidized with air plasma to generate a hydrophilic surface. A solution of water-soluble material was added to the microwells forming Wenzei-siate wetting on the surface. Excess liquid was removed by aspiration. Upon drying, a conforaial coating of solid material was generated inside the microwells.
- PBS Phosphate buffered saline
- Solid sugar polyois such as D-glucose and D-sorbitol
- Solid sugar polyois are preferred materials for the sacrificial residue as they rapidly dissolve in water and are biocompatible
- a PDMS microwell array was welted with an aqueous glucose solution (37% volumetric concentration) and the excess volume above the wells was then removed. After solvent evaporation, a conformal coating of solid glucose lined the microwell walls and floor ( Figure 2).
- the glucose layer appeared to coat only a portion of the microwell walls and floor ( Figure 2), Lower glucose concentrations (22%) resulted in even lower coverage of the microweU surface.
- the angle of the glucose layer on the side wall was also steeper at the lower glucose concentrations.
- a preferred embodiment is to use a glucose solution with c > 33%, for a structured surface possessing microcavities with a wide range of sizes (10 um 3 mm) and depths.
- the glucose coating alters both ⁇ for the side wall and ⁇ for the well, which facilities the rewetting of the microwells by water. Since water can rapidly dissolve glucose, its dissolution guides the rewetting of the microwells (Figure 3A).
- PDMS microwell arrays D - 50 ⁇ , H ⁇ 55 ⁇
- Figure 3B shows the wetting on PDMS microwells with glucose priming (left panel) and without glucose priming (right panel). For microwells without glucose priming, air bubbles formed in microwells.
- microwells primed with a 37% glucose solution no air bubbles formed. This anti-bubble function was effective for 4 months, the longest storage time tested to date, suggesting that the changes in ⁇ and ⁇ were successful in maintaining wettability over time.
- a fluorescently doped glucose solution (37% glucose with 200 ⁇ ig/mL TRITC-dextran. 0.5 MD) was used to prime a PDMS microwell array (microwells with D ⁇ 200 ⁇ , H - 55 ⁇ ) one month prior to the experiment. The loss of fluorescence in the well was then tracked over time to follow glucose dissolution.
- a source of the change in ⁇ is the presence of the glucose coating which creates a hydrophilie sacrificial residue in contact with the gas-entrapping features of the PDMS microfabricated device such that the water rapidly and entirely wets the structured surface of the device.
- the glucose layer also prevents the hydrophobic recovery of the PDMS, thus facilitating the spread of the aqueous solution into the cavity near the edges of the glucose layer.
- the contact angle of PDMS films was evaluated at varying times after priming with glucose. PDMS films were oxidized with plasma and primed with 37% or 0% glucose solutions spread over the surface and dried in air.
- the arrays were rinsed with water and dried under a nitrogen stream, and the contact angle was measured.
- An attenuated total reflectance (ATR)-FTIR spectrometer ( icolet iSl ' O, Thermo Scientific) was used to confirm the absence of glucose residue on the PDMS surfaces ( Figure 6).
- ATR attenuated total reflectance
- FTIR spectrometer icolet iSl ' O, Thermo Scientific
- microfluidic devices Similar to microwell arrays, air bubbles can be trapped in comers and dead ends of microfluidic channels (Figure 4A), To demonstrate the dissolution guided wetting in the comers and dead ends of microfluidic channels, microfluidic devices were built by molding PDMS channels from a master and then bonding it with glass slides through plasma oxidation. Immediately after bonding the channel was primed with glucose or sorbitol solution. Due to the hydrophilic nature of the freshly oxidized PDMS surface, both the sugar solutions wet the entire channel quickly, even in corners and dead ends. The sugar solution was removed by purging the channel with nitrogen and aspiration from the reservoir. After purging, residual sugar solution remained trapped in the corners and dead ends.
- the coverage of glucose priming in a microwell may be estimated by the concentration of the glucose solution used. Assuming the height of the liquid layer above the rim of the microwell was negligible, the total volume of glucose solution loaded into each microwell was:
- h is the height of microwell above solid glucose. If the volumetric concentration of glucose is , then
- the microcavities of a microfabricated device can be full primed by using a glucose solution with e > 33%, even for a surface possessing microcavities with a wide range of sizes (10 p.m ⁇ 3 mm) and depths.
- Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy is a surface-sensitive diagnostic technique which can detect a trance amount of molecules on the top surface (0.5 - 5 ⁇ ) of a sample.
- a flat PDMS sample was oxidized with plasma for 2 min and then primed with a thin layer of glucose or sorbitol in the same way as was used to prime microwell arrays.
- glucose and sorbitol are neutral molecules without any charged and reactive functional groups, so that they are unlikely adsorbed on the PDMS surface via electrostatic or covalent interactions. Because no residue is left in chips, glucose and sorbitol are ideal sacrificial residues for guiding wetting of water (or aqueous solution) in microcavities, corners and dead ends.
- glucose has been shown to be effective to cover the PDMS microcavities and guide their wetting.
- PDMS has the most rapid hydrophobic recovery (V. Jokinen et -at, Biomicrofluidics, 2012, 6, 016501 (2012)). Therefore, dissolution guided wetting using a glucose sacrificial residue on microweils made with other materials such as polystyrene should be as effective as, if not easier than, in PDMS.
- a microwell array was fabricated from polystyrene by our recently reported soft lithography micromolding technique (Y.
- the wells had a diameter of 50 ⁇ and a height of 55 ⁇ .
- the polystyrene microwell array was oxidized with air plasma for 2 rain, primed with a 37 vol% glucose solution in the same way as with microwell arrays formed from PDMS. After priming, the microweils were covered with glucose ( Figure 7). After storage at room temperature for 7 days, water was added to the polystyrene microwell array to test the rewetting guided by glucose. Water quickly (-20-30 s) and completely dissolved the glucose and no air bubbles were trapped in the microweils ( Figure 7).
- sorbitol Dissolution guided wetting using sorbitol as the sacrificial residue in PDMS mierowells has been successfully achieved.
- the wells have a diameter of 50 pm and a height of 55 pra.
- the PDMS microwell array was oxidized with air plasma for 2 min, primed with a 40 vo1% sorbitol solution and dried in air. After priming, the mierowells were covered with sorbitol (Fig, S4). After storage at room temperature for 7 days, water was added to the PDMS microwell array to test the rewetting guided by sorbitol. Water quickly (-20-30 s) and completely dissolved the sorbitol and no air bubbles were trapped in the mierowells ( Figure 7).
- sorbitol functions as effectively as glucose in guiding rewetting in mierowells.
- An additional advantage of sorbitol over glucose is its high solubility in water.
- the solubility of sorbitol in water is 220 g / 100 mL water (equivalent to 59,6 vol%, which is much higher than that of glucose (91 g / 100 mL water, equivalent to 37.1 voi%). Sorbitol 's higher solubility is useful in filling deep microcavities or to guide wetting in dead ends in icrofluidic devices.
- microfluidic chips built by molding PDMS channels from a master mold and then bonding it with glass slides through plasma oxidation ( Figure la).
- a monosaccharide solution in some experiments, the monosaccharide was mixed with 200 ug/mi, TRITC dextran was added to one reservoir for the microfluidic channel ( Figure lb). Due to the hydrophilic surface of the freshly plasma bonded PDMS, the solution spontaneously wet the entire channel withi a few minutes, even in corners and dead ends without trapped air bubbles.
- a sacrificial residue is applied in contact with gas-entrapping features on native, hydrophobic structured surfaces of a microfabricated device.
- the shape of the sacrificial residue deposited depends on the mterfacial property of the structured surface and the solution comprising the sacrificial residue material (Fig. 10- A), in microcavities, a parabolic shaped residue is formed when the solution can wet the solid with small contact angle ⁇ .
- a fla column shape is formed when the solution cannot wet the solid with a large contact angle ⁇ (in other words, the solution dewets on the structured surface).
- PDMS is used with a 25 wt% glucose aqueous solution as the examples for the substrate of a microfabricated device having a structured surface and glucose in solution as the sacrificial residue material, respectively.
- the native PDMS surface is hydrophobic which tends to trap air bubbles in microcavities and other gas-entrapping features.
- the PDMS surface can be oxidized with plasma treatment to change its surface to be hydrophilic.
- a 25 wt% glucose solution is immediately added to the hydrophilic PDMS surface.
- glucose forms a parabolic shape in microcavities (Fig. 10-B), which can effectively guide wetting when water is added to the surface.
- the parabolic shape is caused by the hydrophilic PDMS surface, on which the glucose aqueous solution wets and forms a small contact angle (0 ⁇ 9O°).
- glucose forms a fiat, column shape in PDMS microcavities (Fig. 10-C). This is caused by the hydrophobic PDMS surface, on which the glucose aqueous solution dewets and forms a large contact angle ( ⁇ >90°). This fiat, column shape is not effective in guiding wetting in microcavities.
- organic solvents that are compatible with PDMS are ethanol, isopropanol. dimethylformamide, gamma-butyrolac ' tone (GBL), gamma-va erolaetone, etc.
- Organic solvents have much lower surface tension than water (72.8 dynes/cm), for example, ethanol (22.4 dynes/cm), isopropanol (23,0 dynes/cm).
- a microraft array such as is described in Ailbritton et al, Array of Micromolded Structures for Sorting Adherent Cells
- PCT Application No. PCT/US2011/025018 filed February 16, 2011, herein incorporated by reference is composed of a large number of micron-scale elements made from rigid plastics such as polystyrene, termed rafts, positioned at the bottom of microwelis made from, polydimethylsiloxane (PDMS).
- PDMS polydimethylsiloxane
- glucose was used as a sacrificial material and was deposited on the microraft array by applying a 40 wt% glucose solution on the plasma- oxidized microraft array followed by aspiration to remove excess solution and drying in air (Fig. 2-B-i).
- the glucose coated raft, array can be stored under ambient conditions for at least weeks to months. Even after sufficient time (2 weeks after plasma treatment and deposition of glucose residue) for the PDMS to recover its hydrophobic surface, the dissolution of glucose effectively guided wetting in wells when water was added (Fig, 11-B-ii) as shown by complete absence of air bubbles on the array after water addition (Fig. 11-B-iU),
- a simple method has been described herein that prevents or eliminates the formation of gas bubbles in gas -entrapping features of microfabricated devices, thus solving a common problem encountered when fluids are added to such devices for a variet of lab-cm- a-chip applications.
- the method involves priming the structured surfaces of the crOfabricated device through the application of a sacrificial residue that achieves the dissolution guided wetting of the gas-entrapping features upon introduction of a suitable fluid for the intended use of the device.
- Microfabricated devices thus primed can be kept in dry storage for a prolonged period without loss of efficacy of the dissolution guided wetting. Gas bubble formation was prevented by simply adding a suitable solvent or solution to the device to dissolve the sacrificial residue.
- Dissolution guided wetting can also be achieved with microfabricated devices having hydrophobic structured surfaces by selecting hydrophobic solvents and suitable solutes as the sacrificial residue.
- the method is applicable to a variety of polymer-based, lab-on-a-chip products with gas-entrapping features including microwell arrays and enclosed microiluidic systems where surface wetting is particuiarly challenging,
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